Increase in proton RBE in the last few millimeters of the SOBP (Spread Out Bragg Peak) as observed in intestine (preliminary data)

Reporter: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 13, 2006

Presenter: John Gueulette, PhD
Affiliation: Universite catholique de Louvain, Brussels, Belgium
Other Authors: Joel Martinez, Blanche-Marie De Coster, Julyan Symons, Jacobus Slabbert


  • The RBE (relative biological effectiveness) of proton beam radiotherapy is generally accepted to be about 1.1 compared with x-rays (RBE = 1.0), and doses are scaled accordingly
  • In vitro measurement in cell culture have suggested that the RBE of protons is 6-10% higher at the distal edge of the SOBP
  • This study attempted to use an in vivo model to measure the RBE in the last few millimeters of the SOBP
  • Because whole mouse irradiation would not provide the spatial resolution needed for these measurements, the authors developed a method to externalize a loop of bowel, radiate the loop with protons at different points along the SOBP, and assaying the RBE using the small intestinal crypt regeneration assay

Material and Methods

  • Experimental Setup:
    • A part of the jejunum was externalized under anesthesia. The segment was position perpendicularly to the beam axis with the center of the lumen at the very end of the SOBP. Plastic was placed proximal to the hanging instestine in the build-up region and the cavity containing the hanging intestine was filled with water.
    • A 200 MeV clinical proton beam was used at iThemba LABS ( South Africa ) was used to irradiate the intestines at different doses
    • To determine the relative change at the end of the SOBP, intestines were placed both in the middle of a 7-cm SOBP and 2 mm proximal to the fall-off region.
    • Additionally, whole mouse radiation in the middle of the SOBP was used as an additional control to determine the effect in the middle of the SOBP.
    • After treatment, the intestine was re-internalized and the mice were sacrifice 3.5 days later
  • Mice: 4 mice per dose at 7 doses with 3 dose-effect relations (84 mice total)
  • Assay: Radiated intestines were fixed, serially cut, and stained. Biological effectiveness was expressed as the number of regenerating crypts per circumference


  • The RBE at the end of the spread out Bragg peak was 10% higher than in the middle

Author's Conclusions

  • This in vivo system confirmed the observation that the RBE is about 10% higher at the end of the SOBP
  • The authors recommend that proton radiotherapy treament planning should take this into account, namely by reducing the dose slightly at the distal tail of the SOBP

Clinical and Scientific Implications

  • There is an increased RBE of the distal edge of proton therapy beam profiles
  • This may be important when assessing toxicities in tissues just distal to tumors, especially in critical late reacting tissues such as the spinal cord
  • As noted in several questions, it would be difficult to systematically implement a standard dose decrement to account for the difference in RBE at the tail of the SOBP.
  • More data in different biological systems is needed to confirm this important result